title: A novel flavonoid isolated from the steam-bark of Ulmus wallichiana planchon stimulates osteoblast function and inhibits osteoclast and adipocyte differentiation.
abstract: (2S,3S)-Aromadendrin-6-C-β-d-glucopyranoside (AG) is a novel flavonol isolated from the extract of Ulmus wallichiana (Himalayan Elm). Extract of U. wallichiana is used as a traditional medicine for rapid fracture repair in India. We characterized the mechanism of action of AG in mouse bone cells by investigating its effect on the precursors of osteoblasts, osteoclasts and adipocytes. At nanomolar concentrations, AG increased differentiation of preosteoblasts obtained from neonatal mouse calvaria. The gene expression of osteogenic markers, including runt-related transcription factor 2 (Runx-2), bone morphogenetic protein-2 (BMP-2), type I collagen and osteocalcin were elevated in the preosteoblasts. The extracellular matrix mineralization was higher in preosteoblast and bone marrow cells when AG was present in the medium. Furthermore, AG protected the differentiated osteoblasts from serum deprivation-induced apoptosis, and increased the expression of the anti-osteoclastogenic cytokine, osteoprotegerin. It inhibited osteoclast differentiation of bone marrow precursor cells to osteoclasts in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and monocyte/macrophage-colony stimulating factor (M-CSF). Additionally, in 3T3-L1 preadipocytes, AG decreased the expression of genes involved in adipogenesis, including peroxisome proliferator-activated receptor gamma (PPARγ), sterol regulatory element binding protein (SREBP) and CCAAT/enhancer-binding protein alpha (CEBP/α), and induced apoptosis of differentiated adipocytes. Induction of adipogenic differentiation was also inhibited in the presence of AG. AG exhibited no estrogenic/antiestrogenic effect. Together, our data show that AG has potent osteogenic, anti-osteoclastogenic and anti-adipogenic effects, which may translate to a better skeletal outcome in postmenopausal osteoporosis.
authors.affiliation: Division of Endocrinology, Central Drug Research Institute (Council of Scientific and Industrial Research), Chattar Manzil, P.O. Box 173, Lucknow, India.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Swarnkar
authors.forename: Kunal
authors.initials: K
authors.lastname: Sharan
authors.forename: Jawed A
authors.initials: JA
authors.lastname: Siddiqui
authors.forename: Bandana
authors.initials: B
authors.lastname: Chakravarti
authors.forename: Preeti
authors.initials: P
authors.lastname: Rawat
authors.forename: Manmeet
authors.initials: M
authors.lastname: Kumar
authors.forename: Kamal R
authors.initials: KR
authors.lastname: Arya
authors.forename: Rakesh
authors.initials: R
authors.lastname: Maurya
authors.forename: Naibedya
authors.initials: N
authors.lastname: Chattopadhyay
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects*; D050156:Adipogenesis / Q000187:drug effects*; D000469:Alkaline Phosphatase / Q000096:biosynthesis; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D047309:Flavones / Q000302:isolation & purification* / Q000494:pharmacology; D005419:Flavonoids / Q000302:isolation & purification* / Q000494:pharmacology*; D006027:Glycosides / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D024301:Plant Bark / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry; D034403:Ulmus / Q000737:chemistry*
chemical_list: D047309:Flavones; D005419:Flavonoids; D006027:Glycosides; C554991:aromadendrin 3-O-beta-D-glucopyranoside; D000469:Alkaline Phosphatase